Self-Reported Functional Vision in USH2A-Associated Retinal Degeneration as Measured by the Michigan Retinal Degeneration Questionnaire.

Purpose: The purpose of this study was to evaluate self-reported functional vision (FV) and the impact of vision loss in patients with USH2A-associated retinal degeneration using a patient-reported outcome (PRO) measure, the Michigan Retinal Degeneration Questionnaire (MRDQ), to correlate MRDQ scores with well-established visual function measurements. Design: An observational cross-sectional study (n = 93) of participants who had Usher Syndrome Type 2 (USH2, n = 55) or autosomal recessive non-syndromic retinitis pigmentosa (ARRP; n = 38) associated with biallelic variants in the USH2A gene. Methods: The study protocol was approved by all ethics boards and informed consent was obtained from each participant. Participants completed the MRDQ at the 48-month study follow-up visit. Disease duration was self-reported by participants. One-way ANOVA was used to compare subgroups (clinical diagnosis, age, disease duration, and full-field stimulus threshold [FST] Blue-Red mediation) on mean scores per domain. Spearman correlation coefficients were used to assess associations between MRDQ domains and visual/retinal function assessments. Results: Of the study sample, 58% were female participants and the median disease duration was 13 years. MRDQ domains were sensitive to differences between subgroups of clinical diagnosis, age, disease duration, and FST Blue-Red mediation. MRDQ domains correlated with static perimetry, microperimetry, full-field stimulus testing, and best-corrected visual acuity (BCVA). Conclusions: Self-reported FV measured by the MRDQ, when applied to USH2 and ARRP participants, had good distributional characteristics and correlated well with visual function tests. MRDQ adds a new dimension of understanding on vision-related functioning and establishes this PRO tool as an informative measure in evaluating USH2A outcomes.

Benefits of thermal and distance-filtered imaging for wayfinding with prosthetic vision.

Visual prostheses such as the Argus II provide partial vision for individuals with limited or no light perception. However, their effectiveness in daily life situations is limited by scene complexity and variability. We investigated whether additional image processing techniques could improve mobility performance in everyday indoor environments. A mobile system connected to the Argus II provided thermal or distance-filtered video stimulation. Four participants used the thermal camera to locate a person and the distance filter to navigate a hallway with obstacles. The thermal camera allowed for finding a target person in 99% of trials, while unfiltered video led to confusion with other objects and a success rate of only 55% ([Formula: see text]). Similarly, the distance filter enabled participants to detect and avoid 88% of obstacles by removing background clutter, whereas unfiltered video resulted in a detection rate of only 10% ([Formula: see text]). For any given elapsed time, the success rate with filtered video was higher than with unfiltered video. After 90 s, participants' success rate reached above 50% with filtered video and 24% and 3% with normal camera in the first and second tasks, respectively. Despite individual variations, all participants showed significant improvement when using the thermal and distance filters compared to unfiltered video. Adding a thermal and distance filter to a visual prosthesis system can enhance the performance of mobility activities by removing clutter in the background, showing people and warm objects with the thermal camera, or nearby obstacles with the distance filter.

Functional Vision in Patients With Biallelic USH2A Variants.

PURPOSE: To describe functional vision (FV) and investigate the relationship between FV, visual acuity (VA), and hill of vision (VTOT) at baseline in patients with biallelic USH2A variants. DESIGN: Multicenter, international, cross-sectional study. METHODS: In individuals with biallelic disease-causing variants in USH2A, clinical diagnosis of Usher syndrome type 2 (USH2) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) was based on history of hearing loss and audiology examinations. The VALVVFQ-48 was administered verbally to participants ≥18 years old. VA was measured in both eyes; VTOT was determined from static perimetry in the study eye (better VA). FV scores were calculated using Rasch analysis. RESULTS: Median age of 121 participants (76 with USH2, 45 with ARRP) was 41 years (range: 19-80); 54% were female. FV scores varied from -2.0 to 7.6 logits (median [interquartile range (IQR)]: 2.8 [1.5-3.8]). ARRP and USH2 participants had similar FV scores, both before [mean (95% CI): 2.8 (2.3-3.4) and 2.7 (2.3-3.2), respectively], and after [mean (95% CI): 2.5 (2.1-3.0) and 2.9 (2.6-3.3), respectively; P = .24] adjusting for age, VA, disease duration, and VTOT. VA and VTOT accounted for 29% and 26% of the variance in FV scores, respectively (P < .001 for each). Together, they accounted for 36% of variance observed. CONCLUSIONS: Biallelic USH2A variants were associated with a large range of FV, yet similar in ARRP and USH2, despite hearing loss in USH2. The modified VALVVFQ-48 we evaluated is not ideal for detecting the impact of USH2A-associated retinal degenerations on activities of daily living.

Self-Reported Visual Ability Versus Task Performance in Individuals With Ultra-Low Vision.

Purpose: Visual functioning questionnaires are commonly used as patient-reported outcome measures to estimate visual ability. Performance measures, on the other hand, provide a direct measure of visual ability. For individuals with ultra-low vision (ULV; visual acuity (VA) <20/1600), the ultra-low vision visual functioning questionnaire (ULV-VFQ) and the Wilmer VRI-a virtual reality-based performance test-estimate self-reported and actual visual ability, respectively, for activities of daily living. But how well do self-reports from ULV-VFQ predict actual task performance in the Wilmer VRI? Methods: We administered a subset of 10 matching items from the ULV-VFQ and Wilmer VRI to 27 individuals with ULV. We estimated item measures (task difficulty) and person measures (visual ability) using Rasch analysis for ULV-VFQ and using latent variable signal detection theory for the Wilmer VRI. We then used regression analysis to compare person and item measure estimates from self-reports and task performance. Results: Item and person measures were modestly correlated between the two instruments, with r2 = 0.47 (P = 0.02) and r2 = 0.36 (P = 0.001), demonstrating that self-reports are an imperfect predictor of task difficulty and performance. Conclusions: While self-reports impose a lower demand for equipment and personnel, actual task performance should be measured to assess visual ability in ULV. Translational Relevance: Visual performance measures should be the preferred outcome measure in clinical trials recruiting individuals with ULV. Virtual reality can be used to standardize tasks.

Poster Session: Development and validation of a virtual reality based toolkit to assess functional vision in Ultra Low Vision.

Ultra-Low Vision (ULV) refers to a level of vision that is ≦ 20/1600. There are a growing number of vision restoration treatments that recruit people with ULV or restore vision to the ULV level. At present, limited standardized outcome measures are available to assess visual potential before and after such vision restoration treatments. The ULV toolkit was developed as a standardized outcome measure for people with ULV. Three virtual reality (VR) based modules were developed to assess visual information gathering, hand-eye coordination and wayfinding in people with ULV. Each module consisted of a range of visually guided tasks related to activities of daily life (e.g., direction of motion of cars, flipping a light switch, boarding a train). Each correct/incorrect response was scored as '1'/ '0'. These raw scores were then analyzed to estimate item difficulty (item measure) and person ability (person measure). Item measures showed a wide range of difficulty levels that can be used to evaluate visual performance in people with ULV. Person measures were correlated with estimated logMAR visual acuity as well as completion rates, number of collisions and reaction times. This study bridges a big gap in the field of ULV where little is known about visual potential and usefulness in activities of daily life. VR provides portability and consistency for testing across participants with ULV thereby allowing for standardization of measurements across vision restoration studies.

Development of The Chinese Version of Ultra-Low Vision Visual Functioning Questionnaire-150.

Purpose: The purpose of this study was to develop the Chinese version of Ultra-Low Vision Visual Functioning Questionnaire-150 (ULV-VFQ-150) and evaluate its psychometric function. Methods: A standardized procedure for the translation of ULV-VFQ-150 was carried out, including the forward translation, consistency check, back translation, back review, and coordination. Participants with ultra-low vision (ULV) were recruited for the questionnaire survey. Psychometric characteristics were evaluated using Rasch analysis based on Item Response Theory (IRT), and some items were revised and proofread accordingly. Results: In total, 70 out of 74 responders completed the Chinese ULV-VFQ-150, of which 10 were excluded because their vision did not meet the criterion of ULV. Therefore, 60 valid questionnaires were analyzed (valid response rate = 81.1%). The average age of eligible responders was 49.0 years (standard deviation = 16.0), with 35% female subjects (21/60). The person measures (ability) ranged from -1.7 to +4.9 logits, and the item measures (difficulty) ranged from -1.6 to +1.2 logits. The mean value of item difficulty and personnel ability were 0.00 and 0.62 logits, respectively. The reliability index was 0.87 for items and 0.99 for persons, and the overall fit is good. The items conform to unidimensionality as indicated by principal component analysis of the residuals. Conclusions: The Chinese version of ULV-VFQ-150 is a reliable questionnaire for evaluating both visual function and functional vision in people with ULV in China. Translational Relevance: The Chinese version of ULV-VFQ-150 is a new assessment of the visual function of people with ULV in China.

The validation of inherited retinal disease-specific patient-reported outcome measures in adolescent patients.

PURPOSE: To determine the validity of the validate the adult patient-reported outcome measure tools, the Michigan Retinal Degeneration Questionnaire (MRDQ) and Michigan Vision-Related Anxiety Questionnaire (MVAQ), in adolescent patients with inherited retinal diseases (IRDs). METHODS: Ninety-one adolescent patients diagnosed with IRDs were recruited at the Hospital for Sick Children (University of Toronto) and the Kellogg Eye Center (University of Michigan). The patients were administered the MRDQ, MVAQ, and Patient Health Questionnaire-4 (PHQ-4). Test-retest variability was assessed in eighteen patients within 14 days of the initial administration. Adolescent responses were analyzed for validity and reliability. As a further validation step, comparisons were made to adult data from the original MRDQ and MVAQ studies to ensure consistency in response ranges. RESULTS: The existing MRDQ and MVAQ content and format could accurately detect the impact of IRD on activities of daily living in adolescents with IRDs. No floor/ceiling effects were identified, test-retest reliability was established (r = 0.73-0.86), and no items were excluded after differential item functioning analysis. Domain and trait associations with visual acuity and IRD phenotypes were similar between adolescents and adults. CONCLUSIONS: The MRDQ and MVAQ are psychometrically validated questionnaires for which we have shown validity for use in adolescent patients with IRDs.

Measuring visual information gathering in individuals with ultra low vision using virtual reality.

People with ULV (visual acuity ≤ 20/1600 or 1.9 logMAR) lack form vision but have rudimentary levels of vision that can be used for a range of activities in daily life. However, current clinical tests are designed to assess form vision and do not provide information about the range of visually guided activities that can be performed in daily life using ULV. This is important to know given the growing number of clinical trials that recruit individuals with ULV (e.g., gene therapy, stem cell therapy) or restore vision to the ULV range in the blind (visual prosthesis). In this study, we develop a set of 19 activities (items) in virtual reality involving spatial localization/detection, motion detection, and direction of motion that can be used to assess visual performance in people with ULV. We estimated measures of item difficulty and person ability on a relative d prime (d') axis using a signal detection theory based analysis for latent variables. The items represented a range of difficulty levels (- 1.09 to 0.39 in relative d') in a heterogeneous group of individuals with ULV (- 0.74 to 2.2 in relative d') showing the instrument's utility as an outcome measure in clinical trials.

Measuring visually guided motor performance in ultra low vision using virtual reality.

Introduction: Ultra low vision (ULV) refers to profound visual impairment where an individual cannot read even the top line of letters on an ETDRS chart from a distance of 0.5 m. There are limited tools available to assess visual ability in ULV. The aim of this study was to develop and calibrate a new performance test, Wilmer VRH, to assess hand-eye coordination in individuals with ULV. Methods: A set of 55 activities was developed for presentation in a virtual reality (VR) headset. Activities were grouped into 2-step and 5-step items. Participants performed a range of tasks involving reaching and grasping, stacking, sorting, pointing, throwing, and cutting. Data were collected from 20 healthy volunteers under normal vision (NV) and simulated ULV (sULV) conditions, and from 33 participants with ULV. Data were analyzed using the method of successive dichotomizations (MSD), a polytomous Rasch model, to estimate item (difficulty) and person (ability) measures. MSD was applied separately to 2-step and 5-step performance data, then merged to a single equal interval scale. Results: The mean ±SD of completion rates were 98.6 ± 1.8%, 78.2 ± 12.5% and 61.1 ±34.2% for NV, sULV and ULV, respectively. Item measures ranged from -1.09 to 5.7 logits and - 4.3 to 4.08 logits and person measures ranged from -0.03 to 4.2 logits and -3.5 to 5.2 logits in sULV and ULV groups, respectively. Ninety percent of item infits were within the desired range of [0.5,1.5], and 97% of person infits were within that range. Together with item and person reliabilities of 0.94 and 0.91 respectively, this demonstrates unidimensionality of Wilmer VRH. A Person Item map showed that the items were well-targeted to the sample of individuals with ULV in the study. Discussion: We present the development of a calibrated set of activities in VR that can be used to assess hand-eye coordination in individuals with ULV. This helps bridge a gap in the field by providing a validated outcome measure that can be used in vision restoration trials that recruit people with ULV, and to assess rehabilitation outcomes in people with ULV.

Factors affecting two-point discrimination in Argus II patients.

Two of the main obstacles to the development of epiretinal prosthesis technology are electrodes that require current amplitudes above safety limits to reliably elicit percepts, and a failure to consistently elicit pattern vision. Here, we explored the causes of high current amplitude thresholds and poor spatial resolution within the Argus II epiretinal implant. We measured current amplitude thresholds and two-point discrimination (the ability to determine whether one or two electrodes had been stimulated) in 3 blind participants implanted with Argus II devices. Our data and simulations show that axonal stimulation, lift and retinal damage all play a role in reducing performance in the Argus 2, by either limiting sensitivity and/or reducing spatial resolution. Understanding the relative role of these various factors will be critical for developing and surgically implanting devices that can successfully subserve pattern vision.

Sequential epiretinal stimulation improves discrimination in simple shape discrimination tasks only.

Objective. Electrical stimulation of the retina can elicit flashes of light called phosphenes, which can be used to restore rudimentary vision for people with blindness. Functional sight requires stimulation of multiple electrodes to create patterned vision, but phosphenes tend to merge together in an uninterpretable way. Sequentially stimulating electrodes in human visual cortex has recently demonstrated that shapes could be 'drawn' with better perceptual resolution relative to simultaneous stimulation. The goal of this study was to evaluate if sequential stimulation would also form clearer shapes when the retina is the neural target.Approach. Two human participants with retinitis pigmentosa who had Argus®II epiretinal prostheses participated in this study. We evaluated different temporal parameters for sequential stimulation and performed phosphene shape mapping and forced choice discrimination tasks. For the discrimination tasks, performance was compared between stimulating electrodes simultaneously versus sequentially.Main results. Phosphenes elicited by different electrodes were reported as vastly different shapes. For sequential stimulation, the optimal pulse train duration was 200 ms when stimulating at 20 Hz and the optimal gap interval was tied between 0 and 50 ms. Sequential electrode stimulation outperformed simultaneous stimulation in simple discrimination tasks, in which shapes were created by stimulating 3-4 electrodes, but not in more complex discrimination tasks involving ≥5 electrodes. The efficacy of sequential stimulation depended strongly on selecting electrodes that elicited phosphenes with similar shapes and sizes.Significance. An epiretinal prosthesis can produce coherent simple shapes with a sequential stimulation paradigm, which can be used as rudimentary visual feedback. However, success in creating more complex shapes, such as letters of the alphabet, is still limited. Sequential stimulation may be most beneficial for epiretinal prostheses in simple tasks, such as basic navigation, rather than complex tasks such as novel object identification.

Glow in the dark: Using a heat-sensitive camera for blind individuals with prosthetic vision.

To date, retinal implants are the only available treatment for blind individuals with retinal degenerations such as retinitis pigmentosa. Argus II is the only visual implant with FDA approval, with more than 300 users worldwide. Argus II stimulation is based on a grayscale image coming from a head-mounted visible-light camera. Normally, the 11°×19° field of view of the Argus II user is full of objects that may elicit similar phosphenes. The prosthesis cannot meaningfully convey so much visual information, and the percept is reduced to an ambiguous impression of light. This study is aimed at investigating the efficacy of simplifying the video input in real-time using a heat-sensitive camera. Data were acquired from four Argus II users in 5 stationary tasks with either hot objects or human targets as stimuli. All tasks were of m-alternative forced choice design where precisely one of the m≥2 response alternatives was defined to be "correct" by the experimenter. To compare performance with heat-sensitive and normal cameras across all tasks, regardless of m, we used an extension of signal detection theory to latent variables, estimating person ability and item difficulty in d' units. Results demonstrate that subject performance was significantly better across all tasks with the thermal camera compared to the regular Argus II camera. The future addition of thermal imaging to devices with very poor spatial resolution may have significant real-life benefits for orientation, personal safety, and social interactions, thereby improving quality of life.

The Michigan Retinal Degeneration Questionnaire: A Patient-Reported Outcome Instrument for Inherited Retinal Degenerations.

PURPOSE: To create a psychometrically validated patient-reported outcome measure for inherited retinal degenerations. DESIGN: Qualitative and quantitative patient-reported outcome (PROs) questionnaire development using item response theory validation. METHODS: One hundred twenty-eight patients with a diagnosis of an inherited retinal degeneration at the Kellogg Eye Center (University of Michigan) were recruited and administered a 166-item questionnaire comprising 7 expert-defined domains. The questionnaire was re-administered 4-16 days later to a subset of 25 participants to assess test-retest variability. Graded response models were fit by Cai's Metropolis-Hastings Robbins-Monro algorithm using the R (version 3.6.3) package mirt. Model data were fit to assess questionnaire dimensionality, to estimate item information, and to score participants. Poorly functioning items were removed, and the model was refit to create the final questionnaire. RESULTS: The psychometrically validated PROs measure was reduced to a 59-item questionnaire measuring 7 unidimesnional domains: central vision, color vision, contrast sensitivity, scotopic function, photopic peripheral vision, mesopic peripheral vision, and photosensitivity. A total of 39 items were removed because of poor factor loading, low item information, poor person-ability differentiation, or high item-level interdependence. This novel questionnaire produces a reliable domain score for person ability that does not show significant test-retest variability across repeated administration. CONCLUSIONS: The final PRO questionnaire, known as the Michigan Retinal Degeneration Questionnaire, is psychometrically validated and available for use in the evaluation of patients with inherited retinal degenerations.

CLINICAL CHARACTERISTICS AND NATURAL HISTORY OF RHO-ASSOCIATED RETINITIS PIGMENTOSA: A Long-Term Follow-Up Study.

PURPOSE: To investigate the natural history of RHO-associated retinitis pigmentosa (RP). METHODS: A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP. RESULTS: Based on visual fields, time-to-event analysis revealed median ages of 52 and 79 years to reach low vision (central visual field <20°) and blindness (central visual field <10°), respectively. For the best-corrected visual acuity (BCVA), the median age to reach mild impairment (20/67 ≤ BCVA < 20/40) was 72 years, whereas this could not be computed for lower acuities. Disease progression was significantly faster in patients with a generalized RP phenotype (n = 75; 75%) than that in patients with a sector RP phenotype (n = 25; 25%), in terms of decline rates of the BCVA (P < 0.001) and V4e retinal seeing areas (P < 0.005). The foveal thickness of the photoreceptor-retinal pigment epithelium (PR + RPE) complex correlated significantly with BCVA (Spearman's ρ = 0.733; P < 0.001). CONCLUSION: Based on central visual fields, the optimal window of intervention for RHO-associated RP is before the 5th decade of life. Significant differences in disease progression are present between generalized and sector RP phenotypes. Our findings suggest that the PR + RPE complex is a potential surrogate endpoint for the BCVA in future studies.

The Michigan Vision-Related Anxiety Questionnaire: A Psychosocial Outcomes Measure for Inherited Retinal Degenerations.

OBJECTIVE: We sought to construct and validate a patient-reported outcome measure for screening and monitoring vision-related anxiety in patients with inherited retinal degenerations. DESIGN: Item-response theory and graded response modeling to quantitatively validate questionnaire items generated from qualitative interviews and patient feedback. METHODS: Patients at the Kellogg Eye Center (University of Michigan, Ann Arbor, Michigan, USA) with a clinical diagnosis of an inherited retinal degeneration (n = 128) participated in an interviewer-administered questionnaire. The questionnaire consisted of 166 items, 26 of which pertained to concepts of "worry" and "anxiety." The subset of vision-related anxiety questions was analyzed by a graded response model using the Cai Metropolis-Hastings Robbins-Monro algorithm in the R software mirt package. Item reduction was performed based on item fit, item information, and item discriminability. To assess test-retest variability, 25 participants completed the questionnaire a second time 4 to 16 days later. RESULTS: The final questionnaire consisted of 14 items divided into 2 unidimensional domains: rod function anxiety and cone function anxiety. The questionnaire exhibited convergent validity with the Patient Health Questionnaire for symptoms of depression and anxiety. This vision-related anxiety questionnaire has high marginal reliability (0.81 for rod-function anxiety, 0.83 for cone-function anxiety) and exhibits minimal test-retest variability (ρ = 0.81 [0.64-0.91] for rod-function anxiety and ρ = 0.83 [0.68-0.92] for cone-function anxiety). CONCLUSIONS: The Michigan Vision-Related Anxiety Questionnaire is a psychometrically validated 14-item patient-reported outcome measure to be used as a psychosocial screening and monitoring tool for patients with inherited retinal degenerations. It can be used in therapeutic clinical trials for measuring the benefit of an investigational therapy on a patient's vision-related anxiety.

Improvements in Test-Retest Variability of Static Automated Perimetry by Censoring Results With Low Sensitivity in Retinitis Pigmentosa.

Purpose: We evaluated whether omitting (censoring) points in more severely damaged visual field areas can reduce test-retest variability of static automated perimetry (SAP) in retinitis pigmentosa (RP), as variability creates a significant challenge when monitoring for changes. Methods: Cohort 1 included 27 eyes in 16 RP subjects with visual acuity (VA) ranging from 20/20 to 20/70 who completed Humphrey 10-2 size III SAP, once per visit at three visits. Cohort 2 included 15 eyes in nine RP subjects with VA ≤ 20/60 who completed Humphrey 30-2 size V SAP, twice per visit at three visits. Variability was assessed using 95% coefficient of repeatability (CR) calculations for uncensored (all threshold values and data points included) and censored data. Results: In cohort 1, the uncensored between-visit 95% CR was 11.6 decibels (dB); censoring locations with threshold values of <8 to 20 dB resulted in 31% to 53% reductions in the 95% CR. For cohort 2, uncensored 95% CRs were 8.7 and 8.0 dB for within- and between-visit variability, respectively; censoring <8 to 17 dB resulted in 15% to 41% and 15% to 43% reductions in within-visit and between-visit 95% CRs, respectively. For both cohorts, censoring at higher values yielded slightly less variability, at the expense of discarding data from a greater number of eyes and test locations. Conclusions: For 20/20 to 20/70 VA tested with size III stimuli, censoring lower sensitivity values results in substantially lower test-retest variability, which may help detect true changes for locations without severe baseline loss. Translational Relevance: A rule of thumb for clinical practices using SAP to monitor RP is that longitudinal losses of >9 dB for individual test locations with initial values ≥ 9 dB are likely to be real and meaningful, as they exceed typical variability.

Prosthetic Visual Performance Using a Disparity-Based Distance-Filtering System.

Purpose: At present, Argus II is the only retinal prosthesis approved by the US Food and Drug Administration that induces visual percepts in people who are blind from end-stage outer retinal degenerations such as retinitis pigmentosa. It has been shown to work well in sparse, high-contrast settings, but in daily practice visual performance with the device is likely to be hampered by the cognitive load presented by a cluttered real-world environment. In this study, we investigated the effect of a stereo-disparity-based distance-filtering system on four experienced Argus II users for a range of tasks: object localization, depth discrimination, orientation and size discrimination, and people detection and direction of motion. Methods: Functional vision was assessed in a semicontrolled setup using unfiltered (normal camera) and distance-filtered (stereo camera) imagery. All tasks were forced choice designs and an extension of signal detection theory to latent (unobservable) variables was used to analyze the data, allowing estimation of person ability (person measures) and task difficulty (item measures) on the same axis. Results: All subjects performed better with the distance filter compared with the unfiltered image (P  < 0.001 on all tasks except localization). Conclusions: Our results show that depth filtering using a disparity-based algorithm has significant benefits for people with Argus II implants. Translational Relevance: The improvement in functional vision with the distance filter found in this study may have an important impact on vision rehabilitation and quality of life for people with visual prostheses and ultra low vision.

The use of handheld marker to calibrate a field-programmable gate array based eye tracker for artificial vision system.

Tracking the eye of a blind patient can enhance the usability of an artificial vision system. In systems where the sensing element, i.e. the scene camera that captures the visual information, is mounted on the patient's head, the user must use head scanning in order to steer the line of sight of the implant to the region of interest. Integrating an eye tracker in the prosthesis will enable scanning using eye movements. The eye position will set the region of interest within the wide field-of-view of the scene camera. An essential requirement of an eye tracker is the need to calibrate it. Obviously, off-the-shelf calibration methods that require looking at known points in space cannot be used with blind users.Here we tested the feasibility of calibrating the eye-tracker based on pupil position and the location of the percept reported by the implant recipient, using a handheld marker. Pupil positions were extracted using custom image processing in a field-programmable-gate-array built into a glasses-mounted eye tracker. In the calibration process, electrodes were directly stimulated and the subject reported the location of the percept using a handheld marker. Linear regression was used to extract the transfer function from pupil position to gaze direction in the coordinates of the scene camera.In using the eye tracker with the proposed calibration method, patients demonstrated improved precision on a localization task with corresponding reduction of head movements.

Harmonization of Outcomes and Vision Endpoints in Vision Restoration Trials: Recommendations from the International HOVER Taskforce.

Translational research in vision prosthetics, gene therapy, optogenetics, stem cell and other forms of transplantation, and sensory substitution is creating new therapeutic options for patients with neural forms of blindness. The technical challenges faced by each of these disciplines differ considerably, but they all face the same challenge of how to assess vision in patients with ultra-low vision (ULV), who will be the earliest subjects to receive new therapies. Historically, there were few tests to assess vision in ULV patients. In the 1990s, the field of visual prosthetics expanded rapidly, and this activity led to a heightened need to develop better tests to quantify end points for clinical studies. Each group tended to develop novel tests, which made it difficult to compare outcomes across groups. The common lack of validation of the tests and the variable use of controls added to the challenge of interpreting the outcomes of these clinical studies. In 2014, at the bi-annual International "Eye and the Chip" meeting of experts in the field of visual prosthetics, a group of interested leaders agreed to work cooperatively to develop the International Harmonization of Outcomes and Vision Endpoints in Vision Restoration Trials (HOVER) Taskforce. Under this banner, more than 80 specialists across seven topic areas joined an effort to formulate guidelines for performing and reporting psychophysical tests in humans who participate in clinical trials for visual restoration. This document provides the complete version of the consensus opinions from the HOVER taskforce, which, together with its rules of governance, will be posted on the website of the Henry Ford Department of Ophthalmology (www.artificialvision.org). Research groups or companies that choose to follow these guidelines are encouraged to include a specific statement to that effect in their communications to the public. The Executive Committee of the HOVER Taskforce will maintain a list of all human psychophysical research in the relevant fields of research on the same website to provide an overview of methods and outcomes of all clinical work being performed in an attempt to restore vision to the blind. This website will also specify which scientific publications contain the statement of certification. The website will be updated every 2 years and continue to exist as a living document of worldwide efforts to restore vision to the blind. The HOVER consensus document has been written by over 80 of the world's experts in vision restoration and low vision and provides recommendations on the measurement and reporting of patient outcomes in vision restoration trials.

An update on retinal prostheses.

Retinal prostheses are designed to restore a basic sense of sight to people with profound vision loss. They require a relatively intact posterior visual pathway (optic nerve, lateral geniculate nucleus and visual cortex). Retinal implants are options for people with severe stages of retinal degenerative disease such as retinitis pigmentosa and age-related macular degeneration. There have now been three regulatory-approved retinal prostheses. Over five hundred patients have been implanted globally over the past 15 years. Devices generally provide an improved ability to localize high-contrast objects, navigate, and perform basic orientation tasks. Adverse events have included conjunctival erosion, retinal detachment, loss of light perception, and the need for revision surgery, but are rare. There are also specific device risks, including overstimulation (which could cause damage to the retina) or delamination of implanted components, but these are very unlikely. Current challenges include how to improve visual acuity, enlarge the field-of-view, and reduce a complex visual scene to its most salient components through image processing. This review encompasses the work of over 40 individual research groups who have built devices, developed stimulation strategies, or investigated the basic physiology underpinning retinal prostheses. Current technologies are summarized, along with future challenges that face the field.